1. Field of the Invention
The present invention relates to a method for treating chronic obstructive pulmonary disease (COPD) or lung disease comprising the step of administering the extract of Phyllostachys nigra Munro var. henosis Stapf as an active ingredient to a subject.
2. Description of the Related Art
Chronic obstructive pulmonary disease usually indicates chronic bronchitis or emphysema displaying alveolar damage or both, which is characterized by airway obstruction from bronchus to alveoli. Symptoms of this disease are cough with sputum, which stays long, dyspnea owing to the reduced air current speed resulted from the airway obstruction, and frequent respiratory infection, for example cold. This disease takes the 6th place world-widely in the cause of death list and the 4th place in the US cause of death list. Death rate of this disease in Korea is also rapidly increasing due to the smoking and air pollution, etc. The cause of chronic obstructive pulmonary disease is abnormal chronic inflammation in the lung against toxic molecules or toxic gas induced by the combined action of many factors such as smoking, capitalization and pollution, and respiratory infection, etc, among which smoking is believed to be the most risky factor (National Heart, Lung, and Blood Institute. Morbidity & Mortality: Chartbook on Cardiovascular, Lung, and Blood Diseases. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2003).
Smoking causes inflammation in the airway and in pulmonary parenchyma. The inflammation in the lung produces many kinds of oxidants, and induces proteases and cytokines, which causes the symptoms of chronic obstructive pulmonary disease such as pulmonary emphysemal parenchyma damage, pulmonary arterial remodeling, and pulmonary hypertension (Sethi J M, Rochester C L., Clin. Chest Med. 21:67-86, 2000; D'Armiento J, et al., Cell 71:955-961, 1992; Selman M, et al., Am. J. Physiol. 271:L734-L743, 1996; Segura-Valdez L, et al., Chest 117:684-694, 2000; Finlay G A, et al., Am. J. Respir. Crit. Care Med. 156:240-247, 1997; Hautamaki R D, et al., Science 277:2002-2004, 1997; Wright J L, et al., Inhalation toxicology 10:969-994, 1998).
In particular, pulmonary emphysema has been presumed to be developed when the protease secreted by the inflammatory cells destroys the tissues around. According to recent studies, MMPs secreted in pulmonary macrophages and neutrophils is the important protease that is involved in the destruction of pulmonary parenchyma (Ohnishi K, et al., Lab. Invest. 78:1077-1087, 1998; Frankenberger M, et al., Mol. Med. 7:263-270, 2001).
Some of recent studies confirmed that inflammation and pulmonary parenchyma caused by smoking had not been observed in MMP-12 knock-out mouse (Hautamaki R D, et al., Science 277:2002-2004, 1997), while MMP-12 was up-regulated in the pulmonary macrophages of COPD patient (Finlay G A, et al., Am. J. Respir. Crit. Care Med. 156:240-247, 1997), and MMP-2 and MMP-9 were also up-regulated in BAL fluid of COPD patient (Segura-Valdez L, et al. Chest 117:684-694, 2000). In the meantime, when a MMP inhibitor was administered to the Guinea pig pulmonary parenchyma model induced by smoking, pulmonary parenchyma was alleviated (Selman M, et al., Chest 123:1633-1641, 2003).
However, the destruction of pulmonary parenchyma and hypertension according to COPD are irreversible and progress slowly, and there is no treatment method yet to stop the progress of the disease (National Heart, Lung, and Blood Institute. Morbidity & Mortality: Chartbook on Cardiovascular, Lung, and Blood Diseases. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2003).
The present inventors previously reported that the extract of Phyllostachys nigra Munro var. henosis Stapf increased Th1 reaction and comparatively suppressed Th2 response so that Th1 and Th2 were balanced each other, which was confirmed to be effective in treating asthma (Journal of Ethnopharmacology, Volume 128, No. 1, 2 March (2010), 2010.3.1). One reason that causes COPD is the inhale of irritants represented by smoking. It is considered that allergens are the major cause of asthma. Particularly, smoking makes damages in macrophages and airway epithelial cells and activates neutrophils and CD8 lymphocytes, resulting in alveolar destruction and bronchial wall thickness. On the other hand, in the case of asthma, when mast cells and airway epithelial cells are stimulated, eosinophils and CD4 lymphocytes are activated to cause bronchoconstriction and bronchial hyper-reactivity. So, asthma and COPD are two very different diseases in their causes and development mechanisms.
Phyllostachys nigra Munro var. henosis Stapf indicates the middle part of bamboo prepared by peeling outer skin and drying thereof. The shape is thin membrane or irregular thread like fiber whose width and thickness are irregular and some filaments are 1-11 mm in thickness. The outer face is light green, yellowish green, or light grey or sometimes powder. It has light and elastic fiber like properties. It has been known in Donguibogam that Phyllostachys nigra Munro var. henosis Stapf is effective in treating such symptoms as vomiting, fever, insomnia, and phlegm, etc.
In relation to the prevention and treatment of chronic obstructive pulmonary disease, Korean Patent No. 10-101866 describes that the mixed composition comprising Rehmannia glutinosa, Asparagus cochinchinensis, Schisandra chinensis, moutan cortex radicis, Scutellaria baicalensis, Armeniacae Semen, and Stemona tuberosa roots is effective in treating chronic obstructive pulmonary disease. Korean Patent Publication No. 10-2009-0103239 describes that the composition comprising Vitidis Viniferae Radix extract as an active ingredient is effective in treating asthma or chronic obstructive pulmonary disease. Korean Patent No. 10-0785969 describes that the composition comprising fibroblast growth factor-2 (FGF2) or basic fibroblast growth factor (bFGF) as an active ingredient is effective in preventing or treating asthma and chronic obstructive pulmonary disease. However, there is no report yet about the preventive and therapeutic effect of the extract of Phyllostachys nigra Munro var. henosis Stapf on chronic obstructive pulmonary disease.
Thus, the present inventors tried to develop a natural substance that is effective in treating and preventing chronic obstructive pulmonary disease. In the course of our study, the inventors confirmed that the extract of Phyllostachys nigra Munro var. henosis Stapf reduced the population of macrophages and neutrophils which were increased in bronchoalveolar lavage fluid (BALF) because of chronic obstructive pulmonary disease, lowered significantly the levels of IL-6, TNF-α, IL-1β, MCP-1, and MMP-12 in bronchoalveolar lavage fluid and pulmonary parenchymal tissue or serum which had been rapidly up-regulated owing to chronic obstructive pulmonary disease, reduced inflammatory cells in the tissues around alveola, and reduced significantly the size of alveola which had been enlarged because of the disease. Additionally, the inventors confirmed that the effect of the extract of Phyllostachys nigra Munro var. henosis Stapf was attributed to the blocking of NF-κB signal, which favored for the prevention and treatment of chronic obstructive pulmonary disease, leading to the completion of this invention.